Phenotypes and familiality in speech disorders

言语障碍的表型和家族性

• 批准号: 6908541
• 负责人: H TIMOTHY Bunnell
• 金额: $ 15.94万
• 依托单位: ALFRED I. DU PONT HOSP FOR CHILDREN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6908541
• 关键词: clinical research; computer system design /evaluation; developmental disease /disorder; family genetics; human subject; information systems; linkage mapping; middle childhood (6-11); phenotype; phonology; quantitative trait loci; siblings; speech disorders; speech recognition

DESCRIPTION (provided by applicant): Over the past two decades, significant advances have been made in speech analysis and speech pattern recognition techniques, however, the penetration of these advances into the speech disorders research arena has lagged, and penetration into the clinic is virtually non-existent. We propose to address this lag by adapting and extending speech recognition technology based on Hidden Markov Modeling (HMM) to an analysis of speech from children with speech delay of unknown origin. We will demonstrate the efficacy of this approach by (a) establishing the effectiveness of the proposed analysis techniques in identifying acoustically defined categories of segmental distortions (endophenotypes), (b) examining these acoustically-defined endophenotypes for evidence of heritability and (c) searching for evidence of genetic linkage of the obtained endophenotypes to a region of chromosome 3 that has been implicated in speech disorders. That is, three aims will be addressed: Aim 1: Extension and validation of a new HMM-based approach to the identification and classification of children who are diagnosed with developmental phonological delays. We will develop a new database of information associated with 75 five to nine year old sibling pairs, at least one of whom is diagnosed with SD. Acoustic speech data and perceptual data will provide feature sets in the database for use in identifying possible endophenotypes. Aim 2: Examination of familiarity of acoustic and perceptual measures in developmental phonological disorders to determine whether these measures define heritable quantitative traits. We will assess heritability of the acoustic and perceptual variables as compared with more classically defined speech variables using cluster and sibling correlation analysis to determine whether the more refined phenotypes are more/less heritable that those typically used in speech genetics studies. We hypothesize that the acoustic phenotypes will define a heritable quantitative trait that can be used for future genome screening studies to identify genes involved in speech. Aim 3: Assessment of linkage to chromosome 3 in speech-disordered sibling pairs. Recent studies have shown evidence for linkage of SD to the pericentromeric region of chromosome 3 (Stein et al., 2004). We will use quantitative trait linkage analyses for the speech, acoustic and perceptual phenotypes to determine whether there is evidence for linkage to this region in this patient cohort.

描述（由申请人提供）：在过去的二十年中，语音分析和语音模式识别技术取得了重大进展，然而，这些进展在言语障碍研究领域的渗透却滞后，并且在临床上的渗透实际上还很缓慢。不存在的。我们建议通过调整和扩展基于隐马尔可夫模型 (HMM) 的语音识别技术来分析来自不明原因的语音延迟的儿童的语音，从而解决这一滞后问题。我们将通过以下方式证明这种方法的有效性：（a）确定所提出的分析技术在识别声学定义的片段扭曲类别（内表型）方面的有效性，（b）检查这些声学定义的内表型以获取遗传性证据，以及（c）搜索获得的内表型与与言语障碍有关的 3 号染色体区域的遗传联系的证据。也就是说，将实现三个目标： 目标 1：扩展和验证一种基于 HMM 的新方法，用于对被诊断患有发育语音迟缓的儿童进行识别和分类。我们将开发一个新的信息数据库，其中包含 75 对 5 至 9 岁的兄弟姐妹，其中至少有一个被诊断患有 SD。声学语音数据和感知数据将在数据库中提供特征集，用于识别可能的内表型。目标 2：检查发育语音障碍中听觉和知觉测量的熟悉程度，以确定这些测量是否定义了可遗传的数量性状。我们将使用聚类和同级相关分析来评估声学和感知变量与更经典定义的语音变量的遗传力，以确定更精细的表型是否比言语遗传学研究中通常使用的表型具有更多/更少的遗传性。我们假设声学表型将定义一种可遗传的数量性状，可用于未来的基因组筛选研究，以识别与言语有关的基因。目标 3：评估言语障碍兄弟姐妹与 3 号染色体的连锁。最近的研究显示了 SD 与 3 号染色体着丝粒周围区域连锁的证据（Stein 等，2004）。我们将使用言语、听觉和知觉表型的数量特征连锁分析来确定是否有证据表明该患者队列中与该区域存在联系。